JOURNAL CLUB Presentation

Nighttime Dosing of Doxazosin

Has Peak Effect on
Morning Ambulatory Blood Pressure

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JOURNAL CLUB Presentation
INTRODUCTION
Doxazosin is an alpha-adrenergic antagonist
that is approved for once-daily dosing in the
treatment of hypertension.
The pharmacokinetics of the standard
doxazosin, after oral administration, maximum
plasma drug concentrations are attained in
approximately 2–3 h. Its terminal elimination
half-life is about 22 h. Its long half-life suggested
that doxazosin could be administered as a once-
a-day therapy to manage hypertension.

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 OBJECTIVE
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This study evaluated the effects of a single

daily dose (average 8.9 mg) of doxazosin
(alpha-adrenergic blocker) given at night,
its effects on blood pressure with mild-to-
moderate hypertension, 24-h blood pressure
control using ambulatory monitoring in a
subset of the patients.
METHOD

111 patients (75 men and 36 women) enrolled as two groups.

Group A - consisted of hypertensives who were newly

diagnosed, or who had been previously untreated with
antihypertensive agents for at least 3 months.

Group B - consisted of patients who receiving stable

antihypertensive regimens for the previous 3 months.
STUDY DESIGN
Inclusion criteria Exclusion criteria
History of other significant medical
disorders.
Patients had to be more
Patients with malignant or secondary
than 35 years old. hypertension.
Diagnosis of essential Pregnant or lactating patients.
(primary) hypertension. Patients with orthostatic hypotension
Patients treated with doxazosin or any
other investigational drug within 4
weeks before study entry,
Patients who had donated blood within
30 days before study entry or who
intended to donate during the study.
History of drug or alcohol abuse
STATISTICAL ANALYSIS

The means values were analyzed using paired t tests.

The difference between the effects of treatment
compared using analysis of variance (ANOVA).
Statistical significance was declared when the
associated value was <0.05.
Results are given as the mean ± standard deviation.
RESULT:
CLINICAL OUTCOMES

The 24-h period divided

into four 6-h intervals
(midnight to 5 A M , 6 A M
to 11 A M , noon to 5 P M ,
and 6 P M to 11 PM ).
The respective reductions
were 5 ± 13, 10 ± 12, 8 ± 13,
and 5 ± 12 mm Hg for

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systolic pressure.
RESULT:
CLINICAL OUTCOMES

The respective reductions

were 5 ± 9, 9 ± 9, 6 ± 9,
and 5 ± 9 mm Hg for
diastolic pressure.
The reduction of blood
pressure was highly
significant (P < .001) for
all four periods, for both
systolic and diastolic

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pressure.
RESULT:
CLINICAL OUTCOMES
The greatest reduction (10/9 mm Hg) occurred between
6 A M and 11 A M , and the smallest (5/5 mm Hg) between
6 P M and 11 P M.
The maximum reduction of blood pressure at 8 to 9 A M
was 12 mm Hg for systolic pressure, and 10 mm Hg for
diastolic pressure.
The study showed that the reductions of both systolic
and diastolic pressure were significantly greater (P < .001)
for the 6 A M to 11 A M period than at other times.
DISCUSSION & CONCLUSION

The study show that doxazosin, given once daily at night for a
prolonged period of time, produces a sustained reduction of
blood pressure throughout the day and night.
Although the antihypertensive effect is most pronounced
during the morning hours. It thus has a therapeutic effect of
at least 24-h duration.
A limitation of this study that did not include a placebo
control group.
DISCUSSION & CONCLUSION

Previous study was used in the original evaluation of the time-

course of the effects of doxazosin, which was not based on
ambulatory monitoring, and showed a peak drug level at 2 h.
and a peak effect on blood pressure at about 3 h after dosing.
A finding in the present study, which differed from most other
studies in that the drug was given at night, is that the peak
effect on blood pressure did not occur until 8 to 12 h after
dosing, an interval much longer than would have been
expected from the pharmacokinetics.
 IMPLEMENTATION

Doxazosin considered that the

drug can administration at night
to produces a sustained
reduction of blood pressure
throughout the day and night,
with a significantly effect on the
blood pressure profile.
Reference
Pickering, T., Levenstein, M. and Walmsley, P., 1994.
Nighttime Dosing of Doxazosin Has Peak Effect on Morning
Ambulatory Blood Pressure. The American Journal of
Hypertension, 7(9), pp.844-847.
 CLINICAL TRIAL
LITERATURE EVALUATION

I. Did the trial address a clearly focused issue?

Essential (primary) hypertension patients more than 35 years old.

Single daily dose (average 8.9 mg) of doxazosin

C Mean blood pressure at baseline and Mean blood pressure at study end.

O Mean reductions of blood pressure

 CLINICAL TRIAL
LITERATURE EVALUATION

2. Was the assignment of patients 3. Were all of the patients

to treatments randomised? who entered the trial
properly accounted for
No, this study did not at its conclusion?
randomise because the
selected patients had to be
established with a provider at
one of the designated clinics.
 CLINICAL TRIAL
LITERATURE EVALUATION

4. Were patients, 5. Were the groups

health workers and similar at the start
study personnel of the trial?
"blind' to treatment? There was no difference in
baseline between participants
and the total eligible population.
 CLINICAL TRIAL
LITERATURE EVALUATION

6. Aside from the experimental 7. How precise was the estimate

intervention, were the groups of the treatment effect?
treated equally? The difference between the effects of treatment
compared using analysis of variance (ANOVA).
 CLINICAL TRIAL
LITERATURE EVALUATION

9. Can the results be applied 10. Are the benefits worth

to the local population, or in the harms and costs?
your context?
The results can applied with the local T h e b e n e f i t s wo r t h t h e h a r ms a n d c o s t s
population and in context of Thai patients. should be consider.